Three months treatment with the drug rapamycin increases lifespan, alters cancer prevalence, remodels the microbiome, and improves functional measures of health in middle aged mice in a dose- and sex-dependent manner.
Plants and humans use a shared mechanism, the eukaryotic metabolic sensor TARGET OF RAPAMYCIN protein kinase and its substrate, an RNA-binding protein called LARP1, to coordinate post-transcriptional gene expression.
ATF4 is a metabolic effector of mTORC1 signaling, co-opted to induce gene targets involved in amino acid synthesis, uptake, and tRNA charging, contributing to mTORC1-driven protein and glutathione synthesis.
Modulation of histone levels in gut enterocytes by rapamycin treatment alters chromatin organisation and induces intestinal autophagy through transcriptional regulation to prevent age-related decline in the intestine and extend lifespan.
The cyclic-peptide antibiotic GE23077 inhibits bacterial RNA polymerase through a novel target that exhibits low susceptibility to target-based resistance and that enables synthesis of bipartite inhibitors that are exceptionally potent and refractory to target-based resistance.